Enhancing the therapeutic use of biofilm-dispersing enzymes with smart drug delivery systems

Chelsea R Thorn; P Lynne Howell; Daniel J Wozniak; Clive A Prestidge; Nicky Thomas

doi:10.1016/j.addr.2021.113916

Enhancing the therapeutic use of biofilm-dispersing enzymes with smart drug delivery systems

Adv Drug Deliv Rev. 2021 Dec:179:113916. doi: 10.1016/j.addr.2021.113916. Epub 2021 Aug 8.

Authors

Chelsea R Thorn¹, P Lynne Howell², Daniel J Wozniak³, Clive A Prestidge⁴, Nicky Thomas⁵

Affiliations

¹ University of South Australia, Clinical and Health Sciences, North Tce, Adelaide, SA 5000, Australia; The Basil Hetzel Institute for Translational Health Research, Woodville, SA 5011, Australia; ARC Centre for Excellence in Bio-Nano Science and Technology, Adelaide, SA 5000, Australia; Biofilm Test Facility, Cancer Research Institute, University of South Australia, North Tce, Adelaide, SA 5000, Australia.
² Program in Molecular Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Biochemistry, University of Toronto, Toronto, ON M5S 1A8, Canada.
³ Departments of Microbial Infection and Immunity, Ohio State University, Columbus, OH 43210, USA.
⁴ University of South Australia, Clinical and Health Sciences, North Tce, Adelaide, SA 5000, Australia; ARC Centre for Excellence in Bio-Nano Science and Technology, Adelaide, SA 5000, Australia.
⁵ University of South Australia, Clinical and Health Sciences, North Tce, Adelaide, SA 5000, Australia; The Basil Hetzel Institute for Translational Health Research, Woodville, SA 5011, Australia; ARC Centre for Excellence in Bio-Nano Science and Technology, Adelaide, SA 5000, Australia; Biofilm Test Facility, Cancer Research Institute, University of South Australia, North Tce, Adelaide, SA 5000, Australia. Electronic address: nicky.thomas@unisa.edu.au.

PMID: 34371086
DOI: 10.1016/j.addr.2021.113916

Abstract

Biofilm-dispersing enzymes degrade the extracellular polymeric matrix surrounding bacterial biofilms, disperse the microbial community and increase their susceptibility to antibiotics and immune cells. Challenges for the clinical translation of biofilm-dispersing enzymes involve their susceptibility to denaturation, degradation, and clearance upon administration in vivo. Drug delivery systems aim to overcome these limitations through encapsulation, stabilization and protection from the exterior environment, thereby maintaining the enzymatic activity. Smart drug delivery systems offer target specificity, releasing payloads at the site of infection while minimizing unnecessary systemic exposure. This review highlights critical advances of biofilm-dispersing enzymes as a novel therapeutic approach for biofilm-associated infections. We explore how smart, bio-responsive delivery systems overcome the limiting factors of biofilm-dispersing enzymes and summarize the key systems designed. This review will guide future developments, focusing on utilizing selective and specific therapies in a targeted fashion to meet the unmet therapeutic needs of biofilm infections.

Keywords: Clinical development; Drug delivery systems; Enzyme therapeutics; Glycoside hydrolases; Targeted delivery.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

MeSH terms

Animals
Anti-Bacterial Agents / administration & dosage*
Anti-Bacterial Agents / pharmacology*
Biofilms / growth & development*
Drug Delivery Systems / methods*
Drug Stability
Enzymes / administration & dosage*
Enzymes / pharmacology*
Extracellular Polymeric Substance Matrix / metabolism
Humans

Substances

Anti-Bacterial Agents
Enzymes

Abstract

Publication types

MeSH terms

Substances

Grants and funding